This invention relates to the remediation of endotoxin-contaminated bulk, iodinated non-ionic contrast media. More particularly, the invention pertains to a process for removing endotoxin from such bulk contrast media.
As further background, medical imaging has come to depend to a great extent upon radiographic contrast media. In the X-ray visualization of relatively extensive regions of the human body, for example the cardiovascular system or the space containing the cerebrospinal fluid, large quantities of X-ray contrast agents of high concentration must be injected in order to provide sufficient opacity in the region concerned to produce a clear X-ray image.
As the technology surrounding the production of contrast media has advanced, a problem which has arisen relates to the presence of endotoxins which are produced by bacterial proliferation during the handling of large quantities of aqueous solutions. While the bacteria themselves are easily destroyed in various sterilization procedures, endotoxins are at times left intact.
In this regard, endotoxins have been known and studied for many years particularly in regard to the pathophysiological reactions in animals. For many years it was believed that endotoxin material was contained within gram-negative bacilli cells and was released only upon disintegration of the cell walls. Hence, the material was termed endotoxin. Recent studies, however, suggest that endotoxin is localized at the cell surface of gram-negative bacilli and may be present with viable and killed cells as well as in a free form within a liquid medium.
Endotoxins are known to cause several and varied pathophysiological reactions and have been identified as direct and contributory causes of death of many hospitalized patients. Endotoxins are known to cause febrile reactions in animals with symptoms of extremely high fever, vasodilation, diarrhea, and the like and, in extreme cases, fatal shock. It is also known that endotoxins cause leucocytosis, deleterious changes in carbohydrate and protein metabolism and widespread intravascular clotting by fibrin formation.
Studies have shown that endotoxemia in animals may be caused by gram-negative bacilli primary and secondary infections and/or the employment of intravenous apparatus or solutions contaminated with gram-negative bacilli or endotoxin. The occurrence of endotoxemia from the use of endotoxin-contaminated intravenous or parenteral solutions has recently been recognized as a particular problem in modern hospitals. Since contrast media are often injected into hospital patients in large quantities, the contrast media must first be purified of endotoxin contanimation.
It is presently a common practice in the medical profession to counteract endotoxemia by treatment with massive infusions of antibiotics. However, it has not been shown that antibiotics remove endotoxin other than by controlling gram-negative bacilli. Removal of the bacilli solves the problem of endotoxin production; however, it does nothing to remove the endotoxin that already exists in solution.
In light of this background there exists a need for fast and cost-effective ways to remediate endotoxin-contaminated bulk non-ionic contrast media. The present invention addresses this need.